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Estrogen Regulates the Gonadotropin-Releasing Hormone-Stimulated Secretion of Biologically Active Luteinizing Hormone^*

Department of Internal Medicine, Biodynamics Institute and University of Virginia Health Sciences Center (R.J.U., J.D. V.) Charlottesville, Virginia 22908
the National Institute of Child Health and Human Development, National Institute of Health (M.L.D.) Bethesda, Maryland 20205

Address all correspondence and requests for reprints to: Dr. Johannes D. Veldhuis, Box 202, Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908.

Estrogen produces time-dependent bidirectional effects on the GnRH-stimulated release of immunoactive LH in various species. To examine estrogen’s regulation of biologically active LH secretion in response to pulsatile stimulation by GnRH, we studied estrogen-deficient postmenopausal women basally and during treatment with diethlystilbesterol (DES; 1 mg, orally, daily). Basal and GnRH-stimulated plasma concentrations of bioactive LH were assayed by the in vitro rat interstitial cell testosterone bioassay. GnRH-promoted LH secretory bursts in response to two consecutive stimuli were quantitated by multiple parameter deconvolution analysis. Basal half-lives of LH averaged 171 ± 17 min (immunoactive) and 223 ± 10 min (bioactive). Analysis of variance revealed a significant decrease in mean basal plasma bioactive LH concentrations on days 10 and 30 of DES treatment. Mean serum immunoactive LH concentrations fell similarly. DES significantly increased the halflife of immunoactive LH (days 5 and 10), but did not change that of bioactive LH. GnRH self-priming of bioactive LH secretion (increased LH secretory peak 2 compared to peak 1) was demonstrated, with a maximal value on day 10 of DES treatment. In addition, the ratio of the mass of bioactive to immunoactive LH secreted in response to the first GnRH pulse was significantly enhanced by estrogen on day 5, whereas that after the second pulse of GnRH was significantly suppressed on day 30 of DES. The self-priming action of GnRH on bioactive LH release evident in the presence of oral DES was corroborated in a separate group of six women, who were treated for 30 days with 17β-estradiol via an intravaginally placed Silastic ring.

In conclusion, we infer that estrogen exerts a highly selective effect on the gonadotroph secretory process, such that successive GnRH stimuli result in an increase in the maximal rate and mass of secretion of biologically active LH.

^* This work was supported in part by NIH Grant RR-00847 to the Clinical Research Center of the University of Virginia, CAP RR 00847–15 (14S1; to R.J.U.), American Federation for Aging Research Grant (to R.J.U.), Research Career Development Award 1-KO4-HD-00634 (to J.D.V.), Diabetes and Research Training Center Grant 5-P60-AM-22125–05, the Biodynamics Center, and NIH-supported Clinfo Data Reduction Systems.

Received July 30, 1990.

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